DFRP1增强转录因子Gli1的转录活性促进肝癌细胞增殖的作用和机制研究

DFRP1（DRG家族调节蛋白1）对细胞生长具有重要调控作用，但是与肿瘤的关系未见报道。本课题组前期已证实DFRP1在肝癌组织中高表达，是影响肝癌预后的独立危险因素，体外实验也发现DFRP1能够促进肝癌细胞增殖，并增强Gli1的转录活性。本项目拟进一步在细胞水平研究DFRP1 调控Gli1在肝癌细胞增殖中的作用，并应用荧光素酶报告基因检测及免疫共沉淀等技术研究DFRP1对转录因子Gli1的调控机制；同时在肝癌组织芯片中检测DFRP1、Gli1和受Gli1调控的下游靶基因的表达情况，并进行相关性分析，在临床样本水平验证DFRP1对Gli1的调控。本研究将初步阐明DFRP1促进肝癌细胞增殖的分子机制，为DFRP1及相关分子成为肝癌靶向治疗的靶点提供理论基础。

DFRP1 (DRG family regulatory protein 1) plays an important role in regulation of cell growth, but its function in tumors has not been reported yet. We previously found that the expression level of DFRP1 in hepatocellular carcinoma tissue was higher than that in adjacent non-tumor tissues and it was an independent prognostic predictor for HCC overall survival. Experiments in vitro showed that DFRP1 can promote the proliferation of a HCC cell line, and also enhance transcriptional activity of Gli1. In this study, we will not only validate the effect of DFRP1 on the proliferation of liver tumor cell, but also reveal the function of DFRP1 in regulating the transcriptional activity of Gli1 and the underlying mechanism using co-immunoprecipitation technique and luciferase reporter system. Furthermore, we will detect the expression levels of DFRP1, Gli1 and Gli1 target genes in hepatocellular carcinoma tissue microarray to analyse their relevance and verify the regulation mechanism of DFRP1 on Gli1. This study will reveal the function and mechanism of DFRP1 in promoting HCC cell proliferation and will be helpful to assess the feasibility of DFRP1 and/or related molecules as a potential therapeutic target for HCC therapy.